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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2011-04-04T00:00:00-04:00" class="date-display-single">April 4, 2011</span></p><div class='syndicate'><h1>Genetic Variations Affect Control of the Genome</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Microscope image of red circular areas in 2 cells ">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2011/20110404-variations.jpg?itok=XQ_7WiBd&timestamp=1433349583 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2011/20110404-variations.jpg?itok=MX-ZfBMs&timestamp=1433349583 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2011/20110404-variations.jpg?itok=qsShjKBh&timestamp=1433349583 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2011/20110404-variations.jpg?itok=4ZGuOpF0&timestamp=1433349583 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2011/20110404-variations.jpg?itok=wzt5oe1F&timestamp=1433349583 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2011/20110404-variations.jpg?itok=MX-ZfBMs&timestamp=1433349583" alt="Microscope image of red circular areas in 2 cells " title="Microscope image of red circular areas in 2 cells " />
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</picture><span class="caption">Chromatin (red) in human cells.</span><span class="credit">Matthew Daniels, all rights reserved by Wellcome Images. </span></div>
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</div><p>Genetic variations that lie outside of any known genes can lead to disease. Findings from a new study may help explain why.</p>
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<p>Genome-wide association studies involve scanning the genomes of many people to link single differences in DNA sequence, called single nucleotide polymorphisms (SNPs), with specific diseases or traits. Countless such studies across diverse diseases and conditions have implicated specific regions in the genome. The vast majority of these, however, lie outside of known genes, as 98.5% of our genome doesn't code for proteins.</p>
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<p>To gain insights into these non-coding regions, a team of scientists partly supported by NIH's National Human Genome Research Institute (NHGRI) carried out a genome-wide survey of epigenetic marks — factors that change the way genes are read, or expressed, without changing the DNA sequence itself. The researchers were led by Dr. Manolis Kellis of the Broad Institute and MIT, and Dr. Bradley Bernstein of the Broad Institute, Harvard Medical School and Massachusetts General Hospital. Their study appeared on March 23, 2011, in the advance online edition of <em>Nature</em>.</p>
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<p>The researchers used a comprehensive approach for profiling the state of chromatin — the structure of DNA and protein that forms chromosomes. Changes in chromatin state can affect how and when genes are expressed. The scientists assessed chromatin states across 9 different cell types by mapping the locations across the genome of several epigenetic modifications to DNA, such as methylation and acetylation.</p>
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<p>A computational analysis of the data helped the researchers define 15 distinct chromatin states in 6 broad categories, each corresponding to a different combination of chromatin marks. Three chromatin states were associated with regulatory regions known as promoters, which sit close to genes and allow them to be read. Four chromatin states were associated with regions known as enhancers, which act at a distance and are not always easy to tie to particular genes. Other chromatin states correspond to insulators, which also help regulate active and repressed regions.</p>
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<p>The scientists found that regulatory regions vary greatly in activity depending on the cell type. For example, active promoter states in skeletal muscle were associated with extracellular structure genes, while active promoter states in lymphoblastoid cells were associated with immune response genes. Promoters active in both cells types were associated with general metabolism genes.</p>
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<p>To connect enhancer regions to likely target genes, the researchers compared patterns of chromatin activity with gene expression across the 9 cell types. Patterns of activity for enhancer elements, they found, correlated strongly with patterns of expression for the nearest gene. The scientists were then able to piece together enhancer regulatory networks and their target genes.</p>
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<p>The team used their chromatin state maps to shed light on previously uncharacterized SNPs that have been associated with disease. "Across 10 association studies of various diseases and traits, we found that the associated SNPs significantly overlapped our predicted control region annotations in specific cell types," Kellis says. "This suggests that these DNA changes are disrupting important regulatory elements and thus play a role in disease biology."</p>
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<p>These results give researchers a framework for uncovering genetic regulators that could be potential targets for drug development.</p>
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<p>— by Harrison Wein, Ph.D.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.genome.gov/27532724" target="_top">Epigenomics</a></li><li><a href="https://newsinhealth.nih.gov/2006/February/docs/01features_02.htm" target="_top">Epigenetics: Genes or Environment?</a></li><li><a href="http://www.genome.gov/20019523" target="_top">Genome-Wide Association Studies</a></li></ul>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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